According to Yahoo News, game rangers have found over 40 dead animals, mostly jackals, but also mongeese, foxes and crows in the Addo Elephant National Park, and many more are feared dead.
The motives of the killings are not known, but authorities suspect foul play and have launched an investigation to try to find the culprits.
"This is the worst incident of malicious poisoning of animals inside any national park in South Africa," the park's conservation manager John Adendorff told AFP.
"So far we have found 36 jackals, three crows, two yellow mongoose and two bat-eared foxes."
"We think there are some people who think jackals don't play any role (in nature)," said Adendorff.
Warders are still scouring the vast 186,000 hectare (460,000 acre) national park, which is roughly the same size as the tourist Indian Ocean island of Mauritius.
"We believe there are still many more animals lying dead in the national park," which is close to the southern coastal city of Port Elizabeth.
Adendorff said laboratory tests have confirmed that the animals ingested methomyl, a highly toxic pesticide.
Many more animals are expected to die through secondary poisoning.
"If other animals eat the dead carcasses, they will die also," he said, adding that the poison stays in the soil for up to 90 days so could claim more lives.
The loss of the animals is "priceless, it will take long to recover," he said.